The M60 appears frequently throughout the campaign. It is used to defend the C-130 in "Operation 40" as it is taxiing down a runway under heavy enemy fire, and is one of the starting weapons in "S.O.G." with a version with Extended Mags, or Big Ammo, that can also be picked up in the level. Several mounted M60s also can be used in "S.O.G.". In "The Defector", a mounted M60 can be found at the end of the mission. It is extremely accurate and powerful enough to gib enemies. It is last seen in "Rebirth," being used on Mi-8 helicopters against the advancing CIA soldiers.

The M60 is unlocked at level 21 in multiplayer. It is the only light machine gun that features damage drop-off, while other light machine guns keep the same damage at all ranges. Within close-range, the M60 is one of two fully automatic guns that can achieve two-shot kills (the other being the Skorpion), and can get three-hit kills at all other ranges. It is almost identical to the M60E4 in Call of Duty 4: Modern Warfare with mostly cosmetic differences. The one main difference are its iron sights, which are different to its modern variant. Although it deals high damage, in close ranges the low rate of fire can let the player down against other guns with a higher rate of fire. However, at medium to long ranges, when equipped with a Grip, the M60 can deal huge amounts of damage with high accuracy where other guns such as Assault Rifles would have to fire in bursts to maintain accuracy. Thus, this is an excellent weapon when firing behind cover, such as out of windows on maps such as Nuketown or Berlin Wall.

Due to the gun's large magazine, the user also does not have to worry about reloading often. This is especially true with Extended Mags, which places all 200 carried ammo into the magazine. It is interesting to note that, unlike most weapons, the time for a partial reload and an empty reload are exactly the same, and so for these reasons, the M60 is an excellent choice for players concerned about running out of ammo. Due to the incredibly high damage, large ammo capacity, and manageable fire rate, the M60 has the potential to bring a player to high killstreaks without the need for Scavenger. The time taken to aim down the sights is slow and poor hip fire accuracy, like all other light machine guns. However, either of these problems can be resolved with Sleight of Hand Pro or Steady Aim, respectively. The M60 possesses very high bullet penetration which is boosted even more with Hardened.

Some users may favor Warlord in that this can allow the M60 to have two attachments at the same time, which can come in handy especially considering that the Grip provides such a massive bonus which would be furthered by another attachment. Such a combination could be Grip and Extended Mags, which would allow the player to effectively forget about reloading entirely. As mentioned before, all of the ammunition carried is put into one magazine, which allows for almost 20 seconds of heavy sustained fire. This makes this specific combination very useful for prolonged killstreaks and suppressive fire.

The M60 makes a very brief appearance in Zombies. It is the primary weapon in Dead Ops Arcade for all characters, and can only be replaced by power-ups or if the player receives the Fate of Firepower, upgrading the M60 to a Death Machine permanently. It never needs to reload and never runs out of ammo. It has a different firing sound in Dead Ops Arcade.

The M60 appears in Call of Duty: Black Ops (DS) with its original iron sights, unlike the console/PC versions. It has a low fire rate and very high recoil (in multiplayer, this can be mitigated by using the Nerves of Steel perk), though not as much as the XM22. It has a 100 round box magazine with 200 reserve ammo and a slow reload (fast compared to Light Machine Guns on consoles). In multiplayer, it is unlocked for the allied faction after 150 kills with the XM22, and in Zombies, the M60 can be found in the Mystery Box. It looks very similar to the MG4 despite the ammo being placed below the gun. It is found only twice in the campaign, and it is always more or less hidden.

Also, in "The Defector" when the player is waiting for the boat to arrive, there is a undeleted M60 that fires area-of-effect rounds. It is right by the original M60, by the car.

Before a recent patch, if the player puts a Red Dot Sight on the M60, its pickup text reads "M60 Reflex Sight" instead of "M60 Red Dot Sight" due to a coding error. The reverse is also true; equipping a Reflex Sight names it as the "M60 Red Dot."

In Call of Duty: Black Ops, while the ammo belt does show ammo moving, and being fed into the M60 while firing, it always appears to still have more ammo on the belt, even when the weapon is out of ammo and needs to be reloaded.

When mounted, however, the M60's ammo belt does not move at all while being fired.

The box on the side of the M60 (which holds the ammo belt) is a card-board box with a cut-off top and straps on it. "UP" arrows can be seen on the box.

The carrying handle does not move under firing, but moves during reloading.

When gold camouflage is applied, the entire gun except for the ammo box, will be golden.